Drinking behavior and social context are intimately intertwined, particularly among young adults. Peer relations can promote drinking. At the same time, alcohol consumption promotes social bonding, as in the popular concept of a drinking buddy. Ultimately, to combat unhealthy patterns of social drinking, it is important to understand how ethanol shapes the neurochemistry of affiliative behavior. We have developed a mouse model of conditioned partner preference, and we have obtained pilot data to demonstrate ethanol (EtOH)-induced social preference in female mice. Conditioned partner preference is similar to conditioned place preference, but it incorporates social aspects of approach, recognition, and affiliation. This has relevance to drinking behavior in humans. In our pilot studies thus far, female mice prefer conspecifics with whom they have previously been intoxicated. There is a further interaction of EtOH and estradiol to promote social preference, since EtOH-induced partner preference is enhanced in estrogen- treated ovariectomized females (OVX+E) vs ovariectomized females without estrogen (OVX). The proposed studies will use C57Bl/6 female mice to extend our initial observations. Aim 1a will determine the range of EtOH doses which facilitate conditioned partner preference in OVX, OVX+E, and OVX+E females with progesterone. Aim 1b will examine sex differences in EtOH- induced conditioned partner preference by testing orchidectomized males with and without testosterone. Aim 2 will expand the conditioned partner preference model to test the effects of other drugs of abuse (amphetamines, morphine) on social bonding. Finally, Aim 3 will begin to explore underlying mechanisms for EtOH-induced conditioned partner preference. In this regard, pair bonding and affiliative behavior are sensitive to vasopressin mediated through the vasopressin V1a receptor. Furthermore, the vasopressin system is sensitive to both EtOH and estradiol. Aim 3 will test the ability of a V1a receptor antagonist to block EtOH-induced conditioned partner preference. Together, these studies represent an essential first-step to understand substance abuse and social bonding in mice. PUBLIC HEALTH RELEVANCE: Drinking is a social pastime. Especially among teens, having friends who drink increases drinking behavior. The opposite is also true. That is, drinking promotes social connection. Together, socially-induced alcohol consumption and alcohol-induced social bonding create a potentially-dangerous positive feedback loop with implications for transitioning to unhealthy drinking patterns in social settings. In young women, estrogens may intensify this effect. The proposed studies will investigate ethanol-induced social preference and the effects of ovarian steroid hormones in female mice.